The Kldhc2 gene is located within a locus linked to an automsomal dominant disease that leads
to fibro-fatty replacement of right ventricle myocardium leading to arrythmias (ARVD3; OMIM).
The gene is expressed in
heart
(expression atlas link) and has been implicated in endothelial differentation and
myoblast differentation. Heterozygote null mice have abnormal heart rhythms while
the lethal embryos may have a heart defect.

Acvr2atm1.1(KOMP)Vlcg

Activin receptor IIA is a receptor for activins, which are members of the TGF-beta superfamily involved in diverse biological processes.
Acvr2a mutants are subviable with most pups dying before postnatal day 7. Micro-CT analysis at E15.5 revealed variable penetrance of eye and craniofacial abnormalities. Eye phenotypes varied from normal (Embryo 1- (E1)), to underdeveloped (E2), to cyclopic (E3), to absent (E4). Craniofacial phenotypes varied from normal (E1) to narrow snout (E2), to an elongated snout missing the mandible and tongue (E3, 4) and low set ears (E2, 3, 4).

Cbx4tm1.1(KOMP)Vlcg

Chromobox 4 is in the polycomb protein family that are key regulators of transcription and is reported to be upregulated in lung bud formation and required for thymus development.
Cbx4 mutants showed complete preweaning lethality but were viable at E12.5 and E15.5 with no obvious gross morphological change.
Micro-CT analysis at E15.5 confirmed that
Cbx4tm1.1/tm1.1 mutants had statistically smaller thymus and also revealed smaller adrenal glands and trigeminal ganglia compared to
Cbx4+/+ wildtype embryos.

Whole structural volume differences calculated as a percentage of whole body volume for the left and right thymic rudiment (left) and left and right adrenal (right) of
Cbx4tm1.1/tm1.1 mutant embryos compared to
Cbx4+/+ wildtype embryos. Both organs are significantly smaller in the Cbx4 mutant embryos at an FDR threshold of 5% where the error bars represent 95% confidence intervals.

Tmem100tm1e.1(KOMP)Wtsi

Transmembrane Protein 100 functions downstream of the BMP/ALK1 signaling pathway.
Tmem100 mutants showed complete preweaning lethality and were also lethal at E12.5.
LacZ staining in E12.5 Het embryos was found predominantly in arterial endothelial cells and the heart (arrow) .
OPT analysis at E9.5 revealed that Tmem100 mutant embryos have a large pericardial effusion with cardiac dysmorphology and enlargement (arrow).

Automated MRI analysis of E15.5 Eya4tm1b/tm1b mutants showed that mutant embryos had a statistically smaller
volumes of the cochlea and other tissues compared to
Eya4+/+ wildtype
embryos as highlighted in blue in transverse, coronal, and sagittal sections (false discovery rate (FDR) threshold of 5%).

Lac Z staining at E12.5 showed that Eya4 expression is primarily in the craniofacial mesenchyme, cochleae and outer ear, dermamyotome, and limb.

H&E stained sagittal section through the right cochlea of an
Eya4+/+
wildtype embryo compared to an
Eya4tm1b/tm1b mutant embryo indicated that the mutant
embryo had a hypoplastic cochlea. Higher magnification of the region (indicated by the white box) showed abnormal
perilymphatic (periotic) mesenchyme (PM) in the mutant embryo compared to the wildtype embryo. In the wildtype embryo
the perilymphatic mesenchyme (PM) was rarefied and had multifocal vacuolation (arrow) suggesting normal perilymph
development. In the mutant embryo the perilymphatic mesenchyme (PM) did not show rarefaction and had reduced vacuolation
(arrow) suggesting the cochlear hypoplasia was due to delayed perilymph development.
BL-Bony Labyrinth (cartilage at E15.5), PM-Perilymphatic (periotic) mesenchyme, ML-Membranous Labyrinth, EN-Endolymph

Tox3tm1b(KOMP)Mbp

Tox High Mobility Group Box Family Member 3 is a member of the HMG-box family involved in bending and unwinding DNA.
Tox3 mutants have partial preweaning lethality with 1/3 of the pups dying before P7.
Whole brain MRI at P7 revealed that
Tox3tm1b/tm1b mutants had a much smaller cerebellum (blue) compared to the
Tox3+/+
wildtype mice (as seen in coronal, sagittal, and axial section) and a relatively larger amygdala, thalamus, pons (red)

P3/P7 viability test Tox3

H&E stained coronal section through the brain of a
Tox3+/+ wildtype embryo
compared to a
Tox3tm1b/tm1b mutant embryo indicated that the mutant embryo had a
hypoplastic and dysplastic cerebellum (CE) with markedly reduced fissure formation. Higher magnification revealed
that the transient external granular layer was absent in the
Tox3tm1b/tm1b mutant
mice and the subjacent molecular layer was hypotrophic and irregular in thickness (arrow).

Rsph9tm1.1(KOMP)Vlcg

Radial spoke head protein 9 is a component of the radial spoke head in motile cilia and flagella.
Rsph9 mutants showed partial pre-weaning lethality but viable to P7.
Whole brain MRI and H&E staining of coronal sections of the P7 brain revealed severe hydrocephaly of the left and right lateral ventricles of the Rsph9 mutant.
Coronal section through the nasal region showed that the sinuses of the Rsph9 mutants were filled with pus (asterisks).
Both hydrocephaly and nasal blockage are phenotypes associated with Primary Ciliary Dyskinesia in humans.

Pax7tm1.1(KOMP)Vlcg

Pax 7 is a nuclear transcription factor with DNA-binding activity via its paired domain.
It is involved in specification of the neural crest and is an upstream regulator of myogenesis during post-natal growth and muscle regeneration in the adult.
Pax7 mutants showed complete preweaning lethality.
Micro-CT analysis at E15.5 revealed voxel-wise local volume differences with a larger nasal septum, cavity and capsule (False Discovery Rate <5%) in the E15.5
Pax7tm1.1/tm1.1 mutant embryos compared the wildtype embryos.
LacZ staining at E12.5 showed very strong staining in the medial region of the frontonasal prominence (arrows) where structural changes were found.
LacZ staining was also seen in the midbrain, hindbrain, spinal cord, vertebrae, ribs and neural crest.

Rab34tm1b (EUCOMM)Hmgu/J

Rab34 is a member of the RAS oncogene family, which are small GTPases
involved in intracellular vesicle transport. Rab34 is known to be Golgi-bound, involved in lysosomal positioning.
Rab34 is a potential target of Gli1 and a possible
component of hedgehog signaling. The Rab34 knockout is the first reported null allele for this gene,
resulting in complete preweaning lethality. Phenotypes
include patterning defects, such as polydactyly and facial clefting, as well as abnormal eye
development and severe lung hypoplasia (Fig 1, lu = lung). The mutants are
subviable at E18.5, lethality presumably occurring perinatally.

Bloc1s2tm1.1(KOMP)Mbp

Biogenesis of lysosomal organelles complex 1, subunit 2 is a component of the
BLOC-1 complex, which functions in the formation of lysosome-related
organelles, is implicated in synapse function, and is associated with gamma-
tubulin and the centrosome [1]. Homozygous mutants show complete
preweaning lethality, with embryonic lethality occurring around E15.5. Surviving
mutants at E15.5 show edema, hemorrhage, and abnormal cardiovascular
development (Fig 1). MicroCT datasets of E15.5 embryos also reveal lung
hypoplasia, enlarged right atrium, and compromised right ventricle of the heart
(Fig.1, arrow). Adult heterozygotes show abnormal immunophenotypes.

Gfpt1tm1b(EUCOMM)Wtsi

Gfpt1 encodes glutamine:fructose-6-phosphate amidotransferase 1, which catalyzes the transfer of an amino group from
glutamine onto fructose-6-phosphate. This is the first and rate limiting enzyme of the hexosamine biosynthetic pathway.

Atg3tm1b(EUCOMM)Hmgu

Atg3 is an E2-like protein-conjugating enzyme involved in autophagy broadly expressed during development and in the adult.

Atg3 mutants show complete preweaning lethality with no homozygous pups observed, but they are viable at least until E14.5.
Micro-computed tomography (microCT) imaging at E14.5 revealed homozygous mutant fetuses had cardiovascular abnormalities such
as ventral septum defects (VSD), thick atrio-ventricular valves and a thin myocardium, as well as an enlarged umbilical vein.

Kdm8tm1b(EUCOMM)Wtsi

Kdm8 encodes for lysine (K)-specific demethylase 8, which is predicted to have dual functions as a histone demethylase and as a protein hydroxylase.
The gene is formerly known as Jmjd5.

Kdm8tm1b homozygous mutants showed complete lethality by E12.5. Optical projection tomography (OPT) showed that at E9.5 mutant embryos
appear small in size, remain unturned and that they are developmentally delayed by this stage of gestation. Interestingly.
Kdm8tm1a homozygous mutants can live up to the end of gestation, suggesting that the targeted trap is a hypomorphic allele.

Slc39a8tm1b(EUCOMM)Wtsi

Solute carrier family 39 (metal ion transporter), member 8 encodes a protein that functions as a transporter for several divalent cations.
Mutants show complete preweaning lethality with no homozygous pups observed, but are viable at least until E14.5.
Micro-computed tomography (microCT) imaging at E14.5 revealed mutants were smaller and had cardiovascular abnormalities, such as ventral septum defects.
It also revealed mutants lacked a sternum and had a small chest cavity and liver.

Slc39a8-null mutants are significantly smaller than WT littermates and have smaller livers.

Gygtm1b(KOMP)Wtsi

Glycogenin is an enzyme that converts glucose to glycogen. Glycogenin catalyzes UDP-alpha-D-glucose + glycogenin &rlhar; UDP + alpha-D-glucosylglycogenin. The enzyme is a homodimer of 37 kDa subunits.
Mutations in human GYG1 are associated with Glyocgen Storage Disease XV and Polyglucosan Body Myopathy 2 (OMIM). Homozygous null Gyg mice die between birth and weaning but were found in normal proportions at E18.5. Mutants were indistinguishable from littermates at E12.5, E15.5 or E18.5 but analysis of microCT images revealed obvious cardiac abnormalities, enlarged thymus and abnormal nervous system morphology. This is the first reported Gyg mouse mutant.

Tmem132atm1b(KOMP)Wtsi

Transmembrane protein132a is transmembrane protein of unknown function.
Homozygous null mutants were viable at normal proportions at E15.5 and E18.5 but showed obvious and severe defects that were readibly visible by eye. Embryos had abnormal limb morphology with syndactyly, spina bifida, heart abnormalities. Some mutants were smaller than littermates.